The proposed project is aimed at evaluation of coronary venous retroperfusion methods for treatment of myocardial ischemia. Prior studies have indicated that synchronized retroperfusion (SRP), during coronary artery occlusions can significantly increase myocardial perfusion and function in the profoundly ischemic zone, along with significantly enhancing viability of the jeopardized myocardium. Recently developed professionally manufactured SRP catheters and an integrated pump system are being evaluated for safety and effectiveness, and clinical trials are anticipated as soon as FDA permission is obtained. Preliminary checks in patients indicate that SRP catheters can be appropriately placed without difficulty and within minutes. Substantial interest in mechanisms and applications of SRP was evident at the first International Symposium on Myocardial Protection via the Coronary Sinus, held in Vienna in February 1984. Most recent laboratory emphasis has been on developing new methods and pilot experiments to elucidate retroperfusion mechanisms, and evaluate SRP techniques. Based on this work, a series of research projects are being proposed which are considered important: 1) assessment of factors affecting effective retrograde coronary venous delivery into ischemic myocardium; 2) extension of the state of the art to clinically pertinent timing of SRP followwing coronary occlusion, longer duration SRP treatment, and determination of post-SRP effects; 3) optimization of moderately hypothermic SRP; 4) retrograde infusion of cardioprotective drugs; 5) further study of retroperfusion protection against reperfusion "no reflow" derangements of function, metabolism, rhythm, edema/hemorrhages, and myocardial damage; 6) supplemental data on retrograde coronary venous route lysis of a coronary artery thrombus; 7) examination of alternate coronary venous interventions such as the recently proposed pressure controlled intermittent coronary sinus occlusion; 8) SRP during multiple/repetitive brief coronary artery occlusions, to examine retroperfusion treatment for complex PTCA procedures and other clinical states; 9) study of advantages and limitations of intraoperative cardioplegia via coronary sinus retroperfusion; 10) demonstration of integrated SRP system safety and clinical applicability. The significance of the proposed research is that future clinical SRP applications will be based on comprehensive criteria derived from experimental evaluation of methods over an appropriate range of physiologic conditions.